肠道菌群SCFAs通过活化ILC3改善胰岛素抵抗在胃旁路手术治疗2型糖尿病中的机制研究

2型糖尿病(T2DM)是全球面临的公共健康问题，胃旁路手术(RYGB)能显著控制T2DM的血糖水平，但其机制仍不明确。新近研究表明，肠菌及代谢产物SCFAs参与肠道粘膜免疫，在RYGB改善机体胰岛素抵抗中发挥重要作用，同时肠道中富集的ILC3细胞与肠道粘膜免疫功能密切相关。我们前期研究发现：在T2DM小鼠中，RYGB术后肠道中的ILC3数量明显增加。因此我们推测：RYGB术后胰岛素抵抗改善可能与SCFAs活化ILC3细胞有关。本项目通过体内外研究，旨在探索：①不同长度胆胰袢RYGB术后肠道菌群、SCFAs及各肠段ILC3细胞分布与功能变化；②SCFAs靶向调控Ffar2受体介导ILC3细胞增殖活化，在RYGB改善T2DM机体胰岛素抵抗中的关键作用，并阐明其详细分子机制。此研究有望拓展RYGB治疗T2DM的研究思路，为T2DM的治疗提供新的干预方向及靶点。

Type 2 diabetes mellitus (T2DM) is a global public health problem. Gastric bypass surgery (RYGB) can significantly control the blood glucose level of T2DM, but the mechanism is still unclear. Recent studies have shown that gut microbiota and metabolite SCFAs are involved in intestinal mucosal immunity and play an important role in RYGB improving insulin resistance. At the same time, ILC3s enriched in intestinal tract are closely related to intestinal mucosal immune function. Our previous study found that in T2DM mice, the number of ILC3 in the intestine increased significantly after RYGB. Therefore, we speculated that the improvement of insulin resistance after RYGB may be related to the activation of ILC3 by SCFAs. The purpose of this project is to explore: ① the distribution and functional changes of gut microbiota, SCFAs and ILC3 in different length of biliary-pancreatic limb of RYGB; ② the key role of SCFAs in improving insulin resistance of T2DM by targeting and regulating the proliferation and activation of gut microbiota mediated by Ffar2 receptor, and to clarify its detailed molecular mechanism. This study is expected to expand the research ideas of RYGB in the treatment of T2DM, and provide a new direction and target for the treatment of T2DM.